We suggest that during fatigue, the upper limit of motor neuron firing rates which can be sustained by voluntary effort is regulated to match changes in muscle contractile speed such that they never exceed the minimum required for tetanic fusion (maximum force generation); for in a sustained maximum voluntary contraction (MVC) the falling force cannot be increased by tetanic nerve stimulation despite the decline in the integrated surface EMG (IEMG). Under these conditions, force loss cannot be due to muscle contractile failure. For the adductor pollicis muscle, motor neuron firing rates decline in parallel with the slowing of muscle contractile speed. If a similar relationship is now found for other muscles, and when equal amounts of fatigue are induced by other forms of exercise, a muscle-based reflex regulation is suggested. We shall also attempt to identify the range of firing rates, and their changes, for different fiber types by comparing between muscles and by using exercise protocols where each is selectively and/or sequentially recruited. Reflex control could be mediated by free nerve endings within the muscle which respond to many of the mechanical and metabolic changes which accompany fatigue. These metabolic changes will be monitored and related to MVC firing rates during exercise and ischemic and aerobic recovery. Contractile slowing will also be induced in the absence of fatigue. We postulate that one of the sites of muscle contractile failure is impaired excitation/contraction coupling due to extracellular potassium accumulation. This will be tested by relating changes in the evoked action potential to force loss during fatique and ischemic recovery where restoration of other metabolic events is prevented. These studies will provide important information about factors underlying fatigue in normal subjects, athletes, and in the rehabilitation of debilitated patients.